Preoperative short-course radiotherapy versus combined radiochemotherapy in locally advanced rectal cancer: A multi-centre prospectively randomised study of the Berlin Cancer Society

Department of Surgery and Surgical Oncology, Charité Comprehensive Cancer Center, Charité-Universitätsmedizin Berlin, Berlin, Germany.
BMC Cancer (Impact Factor: 3.36). 03/2009; 9(1):50. DOI: 10.1186/1471-2407-9-50
Source: PubMed


The additional use of radiotherapy has changed the treatment of locally advanced rectal cancer (LARC) dramatically. But a major achievement has been the development of total mesorectal excision (TME) as a surgical standard and the recognition that the surgeon is the predominant prognostic factor. The benefit of preoperative hypofractionated radiotherapy (SCRT; five fractions each of 5 Gy), initially established by the Swedish Rectal Cancer Trial, has been demonstrated in conjunction with TME by the Dutch Colorectal Cancer Group. The concept of combined neoadjuvant radiochemotherapy (conventional radiation of about 50 Gy with chemotherapy) has not been compared over surgery alone with TME. However, the German Rectal Cancer Study Group recently demonstrated that preoperative radiochemotherapy (RCT) was better than postoperative radiochemotherapy in terms of local control.
Patients with histological proven rectal cancer staged T2N+ or T3 are randomized to receive either SCRT (25 Gy in five fractions of 5 Gy) plus TME-surgery within 5 days or RCT (50.4 Gy in 28 fractions of 1.8 Gy, continuous infusion 5-fluorouracil) plus TME-surgery 4-6 weeks later. All patients receive adjuvant chemotherapy (12 weeks continuous infusional 5-FU) and are followed up for 5 years. TME-quality is independently documented by the surgeon and the pathologist. Hypothesis of the study is that RCT is superior to SCRT in terms of local recurrence after five years. Secondary endpoints are overall survival, disease-free survival, complete resection rate (R0 resection), rate of sphincter saving resection, acute and late toxicity (radiation related side effects), and quality of life (including long term bowel function).
Similar long-term survival, local control and late morbidity have been reported for both concepts of preoperative therapy in non-comparative studies. In addition to other ongoing (and recently published) comparative trials we include a larger number of patients for adequate power, apply quality-controlled TME and try to avoid the adjuvant treatment bias by mandatory adjuvant chemotherapy in both groups. Further more, stratification of the initially planned surgical procedure and sphincter-preservation will generate valid evidence whether RCT will allow a less aggressive (sphincter saving) surgical approach.

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Available from: Stephan Koswig
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    • "However, a follow-up study showed that short-course preoperative RT had caused relatively increased risk for postoperative hospitalization due to bowel obstructions and other gastrointestinal (GI) complications [17]. Despite improvements in local control of disease, some studies have demonstrated that preoperative short-course RT for rectal cancer patients does not affect their overall survival significantly [18, 19]. A recent multicenter, randomized study of 1,350 patients with rectal cancer compared short-course preoperative RT and no postoperative treatment with no preoperative RT and a postoperative approach that included chemoRT in selected patients (i.e., those with a positive circumferential margin) and no RT in patients without evidence of residual disease following surgery [20]. "
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    ABSTRACT: A major outcome of importance for rectal cancer is local control. Parallel to improvements in surgical technique, adjuvant therapy regimens have been tested in clinical trials in an effort to reduce the local recurrence rate. Nowadays, the local recurrence rate has been reduced because of both good surgical techniques and the addition of radiotherapy. Based on recent reports in the literature, preoperative chemoradiotherapy is now considered the standard of care for patients with stages II and III rectal cancer. Also, short-course radiotherapy appears to provide effective local control and the same overall survival as more long-course chemoradiotherapy schedules and, therefore, may be an appropriate choice in some situations. Capecitabine is an acceptable alternative to infusion fluorouracil in those patients who are able to manage the responsibilities inherent in self-administered, oral chemotherapy. However, concurrent administration of oxaliplatin and radiotherapy is not recommended at this time. Radiation therapy has long been considered an important adjunct in the treatment of rectal cancer. Although no prospective data exist for several issues, we hope that in the near future, patients with rectal cancer can be treated by using the best combination of surgery, radiation therapy, and chemotherapy in near future.
    Full-text · Article · Aug 2014 · Annals of Coloproctology
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    • "In fact, the maximal response of the radiation occurs only several weeks after its end [10]. For that reason, surgery has been delayed until 8–12 weeks following neoadjuvant CRT [11] [12] [13]. "
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    ABSTRACT: Background: Evaluating impact of tumor regression grade in prognosis of patients with locally advanced rectal cancer (LARC). Materials and methods: We identified from our colorectal cancer database 168 patients with LARC who received neoadjuvant therapy followed by complete mesorectum excision surgery between 2003 and 2011: 157 received 5-FU-based chemoradiation (CRT) and 11 short course RT. We excluded 29 patients, the remaining 139 were reassessed for disease recurrence and survival; the slides of surgical specimens were reviewed and classified according to Mandard tumor regression grades (TRG). We compared patients with good response (Mandard TRG1 or TRG2) versus patients with bad response (Mandard TRG3, TRG4, or TRG5). Outcomes evaluated were 5-year overall survival (OS), disease-free survival (DFS), local, distant and mixed recurrence. Results: Mean age was 64.2 years, and median followup was 56 months. No statistically significant survival difference was found when comparing patients with Mandard TRG1 versus Mandard TRG2 (p = .77). Mandard good responders (TRG1 + 2) have significantly better OS and DFS than Mandard bad responders (TRG3 + 4 + 5) (OS p = .013; DFS p = .007). Conclusions: Mandard good responders had a favorable prognosis. Tumor response (TRG) to neoadjuvant chemoradiation should be taken into account when defining the optimal adjuvant chemotherapy regimen for patients with LARC.
    Full-text · Article · Sep 2013 · International Journal of Surgical Oncology
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    • "A comparative trial, the Berlin Rectal Cancer Trial (BRCT) is still ongoing since 2004. The two regimens of either preoperative shortcourse radiotherapy or conventional radiotherapy are compared with a primary endpoint being the rate of sphincter preservation [64]. In addition, an Australian intergroup trial (TROG, AGITG, CSSANZ, and RACS) was conducted with very similar preoperative treatment protocols. "
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    ABSTRACT: The use of preoperative radiotherapy has resulted in significant downstaging and downsizing of tumor, this in turn facilitated resections permitting sphincter preservation and coloanal anastomosis for patients who would otherwise have not been candidates for this type of surgery as concluded by some small studies. On the other hand, other clinical trials have shown that the effect of radiotherapy on the rate of sphincter preservation is still not clear. Moreover, different modes of radiotherapy have been tested on the rate of sphincter preservation such as pelvic irradiation with or without combination of chemotherapy, short or conventional course radiotherapy, and preoperative or postoperative radiotherapy with different timing intervals of surgery. Unfortunately, these trials didn't clearly answer the question of radiotherapy benefit for the sake of sphincter preserving of rectal cancer patients and the question remained hotly debated.
    Full-text · Article · Apr 2012 · Surgical Oncology
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